OBJECTIVE To investigate the role of Bai Ling Long Zao An Shen formula(BLLZ)in sleep improvement in an environmental stress-induced insomnia rat model and explore its underlying mechanisms.METHODS(1)Component analysis:the chemical constituents of the BLLZ extract were analyzed using ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS).(2)Eval-uation of the sedative and hypnotic effect:① Mice:50 ICR mice were randomly divided into normal control group,BLLZ-L group(5,10 and 20 g·kg-1)and diazepam group(DZP,3 mg·kg-1).After five days of intragastric administration,pentobarbital sodium-induced righting reflex and locomotor activity tests were performed.② Rats:8 SD rats were implanted with electrodes and allowed to recover for seven days before baseline EEG data was collected over 24 h.A crossover design(7 d washout period)was employed,with rats randomly assigned to the DZP(3 mg·kg-1)and BLLZ(20 g·kg-1)group.After five days of treatment,24 h EEG recordings were obtained.(3)Insomnia model and interventions:①8 SD rats were allowed to recover for seven days post-surgery,followed by 6 h(14:00-20:00)baseline EEG recording.A 3×3 crossover design was used to assign rats to model(environmental stress-induced insomnia),model+DZP,or model+BLLZ groups.After five days of treatment,insomnia was induced by frequent cage changes(14:00,16:00 and 18:00),and EEG changes were monitored.(4)Mechanistic study:32 SD rats were randomly divided into the normal control group,model group,and model+DZP group.After five days of treatment,hypothalamic tissues were collected for biochemi-cal analysis.γ-aminobutyric acid(GABA),glutamate(Glu),and dopamine(DA)levels were measured using biochemical kits while γ aminobutyric acid receptor subunit alpha-1(GABAA1),core clock proteins period circadian regulator 2(PER2)and circadian locomotor output cycles(CLOCK)protein expressions were assessed by Western blotting.RESULTS(1)Compared with the normal control group,the sleep latency of BLLZ 10 and 20 g·kg-1 and DZP groups was significantly shortened,and the locomotor activity of BLLZ 20 g·kg-1 and DZP groups was significantly reduced;BLLZ 20 g·kg-1 signifi-cantly increased the total sleep time,slow-wave sleep time,and average duration of sleep in normal rats,and significantly reduced the wakefulness time.(2)The total sleep time and slow-wave sleep time of the model group significantly decreased and the wakefulness time significantly increased compared with baseline.(3)Compared with the model group,the total sleep time and slow-wave sleep time of the model+BLLZ group and the model+DZP group were significantly increased,and the wakefulness time significantly shortened.(4)Compared with the normal control group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly increased and GABAA1 and PER2 protein expres-sion were significantly decreased in the model group;compared with the model group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly decreased,and the expression of GABAA1 and PER2 were significantly increased in the model+BLLLZ group and the model+DZP group.CONCLUSION BLLZ has sedative and hypnotic effects.It can prolong the total slow-wave sleep time by increasing the average duration of slow-wave sleep episodes,thereby increasing the total sleep time and improving environmental stress-induced insomnia.The mechanism may be related to the downregulation of the Glu/GABA ratio and DA levels as well as the enhancement of GABAA1 expressions and the regulation of hypothalamic core clock protein expressions.

Objective To investigate the pharmacological mechanism through which total flavonoids extracted from Xiaobuxin-Tang(XBXT-2)affects neural network activities in the frontal cortex by focusing on the effects of XBXT-2 on the cortical field potentials in the frontal association cortex(FrA)in mice.Methods Cortical electrodes were implanted into the skull of C57BL/6J mice targeting the FrA.After a 7-day recovery period,the mice were administered XBXT-2 intragastrically at a dose of 100 mg/kg,and 1 hour later,local field potential(LFP)in the FrA were recorded for 30 minutes.Spectral analysis of the data was performed using Neuro Explorer software.Changes in the power spectral density of α,β,θ,γ,and δ frequency bands before and after drug administration were analyzed using GraphPad Prism 10.3.Phase-amplitude coupling of θ and γ oscillations was analyzed using Matlab 2021 software.Results It was found that the oral administration of XBXT-2 significantly suppressed high-frequency γ oscillations while simultaneously enhancing θ,β,α,and δ oscillations in FrA of mice compared to the control.Furthermore,XBXT-2 treatment markedly strengthened the phase-amplitude coupling between θ and γ oscillations.Conclusion XBXT-2 possibly affects emotional and cognitive functions by modulating neural network activity in FrA and enhancing θ-γ phase-amplitude coupling in mice.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

OBJECTIVE To investigate the role of Bai Ling Long Zao An Shen formula(BLLZ)in sleep improvement in an environmental stress-induced insomnia rat model and explore its underlying mechanisms.METHODS(1)Component analysis:the chemical constituents of the BLLZ extract were analyzed using ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS).(2)Eval-uation of the sedative and hypnotic effect:① Mice:50 ICR mice were randomly divided into normal control group,BLLZ-L group(5,10 and 20 g·kg-1)and diazepam group(DZP,3 mg·kg-1).After five days of intragastric administration,pentobarbital sodium-induced righting reflex and locomotor activity tests were performed.② Rats:8 SD rats were implanted with electrodes and allowed to recover for seven days before baseline EEG data was collected over 24 h.A crossover design(7 d washout period)was employed,with rats randomly assigned to the DZP(3 mg·kg-1)and BLLZ(20 g·kg-1)group.After five days of treatment,24 h EEG recordings were obtained.(3)Insomnia model and interventions:①8 SD rats were allowed to recover for seven days post-surgery,followed by 6 h(14:00-20:00)baseline EEG recording.A 3×3 crossover design was used to assign rats to model(environmental stress-induced insomnia),model+DZP,or model+BLLZ groups.After five days of treatment,insomnia was induced by frequent cage changes(14:00,16:00 and 18:00),and EEG changes were monitored.(4)Mechanistic study:32 SD rats were randomly divided into the normal control group,model group,and model+DZP group.After five days of treatment,hypothalamic tissues were collected for biochemi-cal analysis.γ-aminobutyric acid(GABA),glutamate(Glu),and dopamine(DA)levels were measured using biochemical kits while γ aminobutyric acid receptor subunit alpha-1(GABAA1),core clock proteins period circadian regulator 2(PER2)and circadian locomotor output cycles(CLOCK)protein expressions were assessed by Western blotting.RESULTS(1)Compared with the normal control group,the sleep latency of BLLZ 10 and 20 g·kg-1 and DZP groups was significantly shortened,and the locomotor activity of BLLZ 20 g·kg-1 and DZP groups was significantly reduced;BLLZ 20 g·kg-1 signifi-cantly increased the total sleep time,slow-wave sleep time,and average duration of sleep in normal rats,and significantly reduced the wakefulness time.(2)The total sleep time and slow-wave sleep time of the model group significantly decreased and the wakefulness time significantly increased compared with baseline.(3)Compared with the model group,the total sleep time and slow-wave sleep time of the model+BLLZ group and the model+DZP group were significantly increased,and the wakefulness time significantly shortened.(4)Compared with the normal control group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly increased and GABAA1 and PER2 protein expres-sion were significantly decreased in the model group;compared with the model group,the Glu/GABA ratio,DA content and CLOCK protein expression were significantly decreased,and the expression of GABAA1 and PER2 were significantly increased in the model+BLLLZ group and the model+DZP group.CONCLUSION BLLZ has sedative and hypnotic effects.It can prolong the total slow-wave sleep time by increasing the average duration of slow-wave sleep episodes,thereby increasing the total sleep time and improving environmental stress-induced insomnia.The mechanism may be related to the downregulation of the Glu/GABA ratio and DA levels as well as the enhancement of GABAA1 expressions and the regulation of hypothalamic core clock protein expressions.

OBJECTIVE To investigate the effect and mechanism of soluble guanylate cyclase stimulator sGC003F on cardiac function in mice with chronic heart failure(CHF).METHODS C57BL/6J male mice were randomly divided into the sham operation(sham)group,transverse aortic constriction induced CHF mouse model group,model+veliciguat(Ver,3 mg·kg-1)group(positive control)and model+sGC003F(3 and 10 mg·kg-1)group.Four weeks after modeling,drugs were ig given,once a day,for 28 d.Echocardiography was used to measure the changes in cardiac function,and the myocardial hypertrophy related indexes were calculated.The levels of serum N-terminal pro-brain natriuretic peptide(NT-pro-BNP),N-terminal pro-atrial natriuretic peptide(NT-pro-ANP),soluble guanylate cyclase(sGC),cyclic guanosine monophosphate(cGMP)and inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and IL-1β were detected by ELISA.The pathological changes of left heart tissue were observed with HE and Masson staining.Image was used to analyze the percentage of fibrosis in cardiac tissus stained with Masson.The activity of superoxide dismutase(SOD),content of malondialdehyde(MDA)in myocardial tissue,and level of nitric oxide(NO)in serum were detected by biochemical detection kits.The protein expression levels of p-mammalian target of rapamycin(p-mTOR),p-protein kinase B(p-Akt),TNF-α and IL-6 in cardiac tissue were detected by Western blotting.RESULTS Com-pared with the sham group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFs)in the model group decreased significantly(P<0.01),the cardiac structure changed significantly,the percentage of myocardial fibrosis increased significantly(P<0.05),so were serum NT-pro-BNP and NT-pro-ANP levels(P<0.01).Compared with the model group,the above indexes of the model+Ver group and the model+sGC003F 3 mg·kg-1 group were significantly improved(P<0.05,P<0.01).The sGC003F 10 mg·kg-1 group had a significant improvement in LVEF,LVFs,and NT-pro-BNP(P<0.01).Compared with the sham group,the serum levels of NO,sGC and cGMP in the model group decreased significantly(P<0.05,P<0.01).Compared with the model group,the serum levels of NO,sGC and cGMP were significantly increased in the model+sGC003F 3 mg·kg-1 group(P<0.01),but only serum cGMP levels were significantly increased in model+Ver and model+sGC003F 10 mg·kg-1 groups(P<0.01).Compared with the sham group,the serum levels of TNF-α,IL-1β and IL-6 in the model group were significantly increased(P<0.05,P<0.01).Compared with the model group,the serum levels of TNF-α,IL-1β and IL-6 were significantly decreased in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),and only the TNF-α level was significantly decreased in the model+sGC003F 10 mg·kg-1 group(P<0.01).Compared with the sham group,the SOD activity of the model group was significantly decreased(P<0.01),but the MDA content significantly increased(P<0.01).Compared with the model group,SOD and MDA were significantly improved in the model+sGC003F 3 mg·kg-1 group(P<0.05,P<0.01),but in the model+Ver group only the SOD activity significantly increased(P<0.05).Western blotting showed that the expressions of p-mTOR,p-Akt,TNF-α and IL-6 protein in myocardial tissue of the model group were significantly higher than in the sham group(P<0.05).Compared with the model group,the expressions of the above proteins in the model+sGC003F 3 mg·kg-1 group were significantly decreased(P<0.05,P<0.01),so were the expressions of TNF-α protein in the model+sGC003F 10 mg·kg-1 group and model+Ver group(P<0.01).CONCLUSION sGC003F can improve cardiac function,and reduce myocardial fibrosis in CHF model mice,which may be related to the inhibition of myocardial oxidative stress and inflammation,and the regulation of NO/sGC/cGMP and AKT/mTOR signaling pathways.

Objective:To investigate the surgical situations and perioperative outcome of pancreaticoduodenectomy in Jiangsu Province and the influencing factors for postoperative 90-day mortality.Methods:The retrospective case-control study was conducted. The clinicopathological data of 2 886 patients who underwent pancreaticoduodenectomy in 21 large tertiary hospitals of Jiangsu Quality Control Center for Pancreatic Diseases, including The First Affiliated Hospital of Nanjing Medical University, from March 2021 to December 2022 were collected. There were 1 732 males and 1 154 females, aged 65(57,71)years. Under the framework of the Jiangsu Provincial Pancreatic Disease Quality Control Project, the Jiangsu Quality Control Center for Pancreatic Diseases adopted a multi-center registration research method to establish a provincial electronic database for pancrea-ticoduodenectomy. Observation indicators: (1) clinical characteristics; (2) intraoperative and post-operative conditions; (3) influencing factors for 90-day mortality after pancreaticoduodenectomy. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(IQR), and comparison between groups was conducted using the Mann-Whitney U test. Count data were expressed as absolute numbers or constituent ratio, and comparison between groups was conducted using the chi-square test, continuity correction chi-square test and Fisher exact probability. Maximal Youden index method was used to determine the cutoff value of continuous variables. Univariate analysis was performed using the corresponding statistical methods based on data types. Multivariate analysis was performed using the Logistic multiple regression model. Results:(1) Clinical characteristics. Of the 2 886 patients who underwent pancreaticoduodenectomy, there were 1 175 and 1 711 cases in 2021 and 2022, respectively. Of the 21 hospitals, 8 hospitals had an average annual surgical volume of <36 cases for pancreaticoduodenectomy, 10 hospitals had an average annual surgical volume of 36-119 cases, and 3 hospitals had an average annual surgical volume of ≥120 cases. There were 2 584 cases performed pancreaticoduodenectomy in thirteen hospitals with an average annual surgical volume of ≥36 cases, accounting for 89.536%(2 584/2 886)of the total cases. There were 1 357 cases performed pancrea-ticoduodenectomy in three hospitals with an average annual surgical volume of ≥120 cases, accounting for 47.020%(1 357/2 886) of the total cases. (2) Intraoperative and postoperative conditions. Of the 2 886 patients, the surgical approach was open surgery in 2 397 cases, minimally invasive surgery in 488 cases, and it is unknown in 1 case. The pylorus was preserved in 871 cases, not preserved in 1 952 cases, and it is unknown in 63 cases. Combined organ resection was performed in 305 cases (including vascular resection in 209 cases), not combined organ resection in 2 579 cases, and it is unknown in 2 cases. The operation time of 2 885 patients was 290(115)minutes, the volume of intra-operative blood loss of 2 882 patients was 240(250)mL, and the intraoperative blood transfusion rate of 2 880 patients was 27.153%(782/2 880). Of the 2 886 patients, the invasive treatment rate was 11.342%(327/2 883), the unplanned Intensive Care Unit (ICU) treatment rate was 3.087%(89/2 883), the reoperation rate was 1.590%(45/2 830), the duration of postoperative hospital stay was 17(11)days, the hospitalization mortality rate was 0.798%(23/2 882), and the failure rate of rescue data in 2 083 cases with severe complications was 6.529%(19/291). There were 2 477 patients receiving postoperative 90-day follow-up, with the 90-day mortality of 2.705%(67/2477). The total incidence rate of complication in 2 886 patients was 58.997%(1 423/2 412). The incidence rate of severe complication was 13.970%(291/2 083). The comprehensive complication index was 8.7(22.6) in 2 078 patients. (3) Influencing factors for 90-day mortality after pancreaticoduodenectomy. Results of multivariate analysis showed that age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment were independent risk factors for 90-day mortality after pancreaticoduodenectomy ( odds ratio=2.403, 2.609, 16.141, 95% confidence interval as 1.281-4.510, 1.298-5.244, 7.119-36.596, P<0.05). Average annual surgical volume ≥36 cases in the hospital was an independent protective factor for 90-day mortality after pancreaticoduodenectomy ( odds ratio=0.368, 95% confidence interval as 0.168-0.808, P<0.05). Conclusions:Pancreaticoduodenectomy in Jiangsu Province is highly con-centrated in some hospitals, with a high incidence of postoperative complications, and the risk of postoperative 90-day mortality is significant higher than that of hospitallization mortality. Age ≥ 70 years, postoperative invasive treatment, and unplanned ICU treatment are independent risk factors for 90-day motality after pancreaticoduodenectomy, and average annual surgical volume ≥36 cases in the hospital is an independent protective factor.

OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.

OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.

Objective:To study the pathogenic spectrum of enterovirus (EV) in the samples of child influenza-like(ILI)cases in Hangzhou city .Methods:In 2019, 1 060 throat swab specimens of ILI cases were collected for serotyping of influenza virus and EVs by real-time RT-PCR. The positive rates of influenza virus and EV in spring, summer, autumn and winter were compared by chi-square test with SPSS16.0 software. Specific primers were synthesized and used to amplify the VP1 fragments of EV. PCR products were sequenced and the results were compared with the reference sequences by using Basic Local Alignment Search Tool (BLAST) to identify the serotypes of isolated EV. The clinical diagnoses of EV positive cases were classified and analyzed.Results:A total of 1 060 specimens were collected and 283(26.70%) were positive for influenza virus, 75(7.08%) were positive for EV, 3(0.28%)were positive for influenza virus and EV. The comparison of positive detection rate of spring, summer, autumn and winter showed that influenza virus were prevalent in winter and spring. EV were mostly popular in the summer months. VP1 sequences of 51 EV were successfully amplified and BLAST analysis revealed that these strains belonged to 10 serotypes, including five serotypes of EV-A species, four serotypes of EV-B species and one serotype of EV-D. The ten serotypes of EV, including coxsackievirus (CV)A2, A4, A5, A6, A9, A10, and echovirus (ECHO)7, ECHO11, ECHO18, and EV-D68 were obtained and the percentages of positive were 16.00%, 16.00%, 5.33%, 12.00%, 5.33%, 1.33%, 1.33%, 5.33%, 4.00% and 1.33%, respectively. The phylogram of EV VP1 sequence showed that 51 EV strains in Hangzhou had different degrees of variation compared with the reference strains. Acute upper respiratory tract infection was the main clinical diagnosis in EV positive children, with 44 cases (58.67%). Acute tonsillitis was followed by 14 cases (18.67%). Followed by herpetic pharyngitis, acute bronchitis, asthmatic bronchitis, pneumonia, accounting for 12.00%, 8.00%, 1.33%, 1.33%, respectively.Conclusions:EV causing influenza-like illness in children in Hangzhou in 2019 belonged to 10 serotypes, CVA2 and CVA4 were the predominant serotypes, and the positive rate of EV detection was higher in summer.

Objective: To determine the epidemic characteristics of respiratory viruses, mycoplasma pneumonia(MP) and chlamydia pneumoniae(CP) in outpatients and hospitalized children with acute respiratory tract infections(ARI), to lay a foundation for the prevention and control of ARI. Methods: From 2011 to 2013, children with ARI, including outpatients and inpatients, were involved in this study. One nasopharyngeal aspirate or throat swab specimen was collected from each patient.Real time PCRs were performed to detect common respiratory tract viruses, MP and CP. Results: At least one pathogen was identified in each of 610 out of 908 patients and the overall positive rate was 67.2%. The positive rate in inpatient(76.7%)was higher than that in outpatient(43.0%) (χ²=94.79, P<0.001). Simultaneous detection of two or more viruses was found in 206 cases.Co-infection was more frequent in inpatients than in outpatients(29.0% VS 6.6%, P<0.001). Significant differences of the detection rate were observed in RSV, PIV, HRV, Flu, human bocavirus (hBoV), adenovirus (AdV), saffold virus(SAFV), MP and CP between the inpatient and outpatient group. Respiratory syncytial virus(RSV)(34.5%) was the most prevalent virus detected among hospitalized children, followed by MP(15.0%)and human rhinovirus(HRV)(14.6%). Whereas adenovirus(AdV) (15.2%)was the most frequently identified virus in the outpatient group, followed by influenza virus(Flu)(11.7%))and PIV(7.8%). Except for RSV and Flu, co-infection of the other pathogens was more frequent than its mono-infection in inpatients. Significant differences of the AdV co-infection rate were observed between the inpatient and outpatient group(χ²=18.90, P<0.001). Compared with mono-infection, co-infection has no significant effect on the clinical presentation. Conclusions The detection rate of respiratory pathogens was higher in inpatients than in outpatients with ARI, and co-infections were more popular in children hospitalized, it may show that co-infection had some correlation with disease severity.